Genomics: Colorectal cancer characterized

The genome-wide characterization of colorectal carcinoma was published online today in the journal, Nature. Nationwide Children’s Hospital was one of several institutions involved in this study. The research analyses 276 tumor samples, and presents new markers for aggressive tumors, along with uncovering an important role for the regulator gene MYC. The team also identify copy number variation in two genes that could be potential drug targets.

Colorectal cancer is the second leading cause of cancer-related deaths in the United States and the data provide a useful resource for understanding this deadly disease. The Cancer Genome Atlas project, of which Nationwide Children’s is a partner, plans to profile genomic changes in 20 cancer types and has published results on two kinds of cancer so far.

In this paper they present an analysis of the exome sequence, DNA copy number, promoter methylation and messenger RNA and microRNA expression in human colorectal carcinoma. In the analysis, 16 percent of the tumors have mutations in DNA repair genes so they are hypermutated - mutation is unusually frequent in these tumors and this can explain why they become resistant to treatment.

The data reveal a remarkably consistent pattern of genomic alteration, and colon and rectum cancers have considerably similar patterns of genomic alteration, with 24 genes significantly mutated. Recurrent copy-number alterations include amplifications of ERBB2 and newly discovered amplification of IGF2, which the authors suggest could be targets for new drugs that could treat colorectal cancer in a targeted way.